Cynthia D. Morris

Trial of calcium to prevent preeclampsia

Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 wome...

A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects

OBJECTIVES This study sought to define 1) the risk of sudden death after operation for common congenital heart defects; and 2) factors associated with an increased risk of sudden death. BACKGROUND Although the prognosis for patients with congenital heart defects is improved by surgical treatment, they remain at a well recognized but poorly defined risk of late sudden death. METHODS This population-based study evaluated all patients < 19 years old undergoing surgical treatment of common forms of congenital heart disease in the state of Oregon between 1958 and 1996. Patients were identified retrospectively through 1958, with prospective biannual follow-up beginning in 1982. The incidence and cause of late sudden death were evaluated for 3,589 patients surviving operation for the following defects: atrial, ventricular and atrioventricular septal defects; patent ductus arteriosus; pulmonary stenosis; aortic stenosis; coarctation of the aorta; tetralogy of Fallot; and D-transposition of the great arteries. RESULTS There were 41 unexpected late sudden deaths during 45,857 patient-years of follow-up, an overall event rate of 1/1,118 patient-years. Thirty-seven of the 41 late sudden deaths occurred in patients with aortic stenosis, coarctation, transposition of the great arteries or tetralogy of Fallot, an event rate of 1/454 patients-years. In contrast, only four sudden deaths occurred among the other defects, an event rate of 1/7,154 patient-years (p < 0.01). The risk of late sudden death increased incrementally 20 years after operation for tetralogy of Fallot, aortic stenosis and coarctation. However, risk was not dependent on patient age at operation or surgical era. The causes of sudden death were arrhythmia in 30 patients, circulatory (embolic or aneurysm rupture) in 7 and acute heart failure in 4. CONCLUSIONS The risk of late sudden death for patients surviving operation for common congenital heart defects is 25 to 100 times greater than an age-matched control population. This increased risk is primarily represented by patients with cyanotic or left heart obstructive lesions. The risk of sudden death appears to be time dependent, increasing primarily after the second postoperative decade.

Blood Pressure Response to Oral Calcium in Persons with Mild to Moderate Hypertension: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

The blood pressure response of 48 hypertensive persons and 32 normotensive persons to elemental calcium (as the carbonate or citrate salt), 1000 mg/d for 8 weeks, was assessed in a randomized, double-blind, placebo-controlled, crossover trial. Compared with placebo, Ca2+ significantly lowered supine systolic blood pressure by 3.8 mm Hg, standing systolic blood pressure by 5.6 mm Hg (p less than 0.02), and supine diastolic blood pressure by 2.3 mm Hg (p less than 0.05) in hypertensive persons. The response in normotensive persons differed significantly from that in hypertensives (p less than 0.03) as their blood pressure was unchanged. Twenty-one (44%) hypertensive and 6 (19%) normotensive persons achieved a reduction in standing systolic arterial pressure of 10 mm Hg or greater. Reported adverse effects were similar between calcium and placebo phases and did not necessitate withdrawal of any patient from the trial. Treatment with 1000 mg/d of oral Ca2+ for 8 weeks represents a safe, well-tolerated, nonpharmacologic intervention that lowers blood pressure in selected patients with mild to moderate hypertension.

Prevalence of Colon Polyps Detected by Colonoscopy Screening in Asymptomatic Black and White Patients

CONTEXT Compared with white individuals, black men and women have a higher incidence and mortality from colorectal cancer and may develop cancer at a younger age. Colorectal cancer screening might be less effective in black individuals, if there are racial differences in the age-adjusted prevalence and location of cancer precursor lesions. OBJECTIVES To determine and compare the prevalence rates and location of polyps sized more than 9 mm in diameter in asymptomatic black and white individuals who received colonoscopy screening. DESIGN, SETTING, AND PATIENTS Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States using a computerized endoscopic report generator between January 1, 2004, and December 31, 2005. Data were transmitted to a central data repository, where all asymptomatic white (n = 80 061) and black (n = 5464) patients who had received screening colonoscopy were identified. MAIN OUTCOME MEASURES Prevalence and location of polyps sized more than 9 mm, adjusted for age, sex, and family history of colorectal cancer in a multivariate analysis. RESULTS Both black men and women had a higher prevalence of polyps sized more than 9 mm in diameter compared with white men and women (422 [7.7%] vs 4964 [6.2%]; P < .001). Compared with white patients, the adjusted odds ratio (OR) for black men was 1.16 (95% confidence interval [CI], 1.01-1.34) and the adjusted OR for black women was 1.62 (95% CI, 1.39-1.89). Black and white patients had a similar risk of proximal polyps sized more than 9 mm (OR, 1.13;95% CI, 0.93-1.38). However, in a subanalysis of patients older than 60 years, proximal polyps sized more than 9 mm were more likely prevalent in black men (P = .03) and women (P < .001) compared with white men and women. CONCLUSION Compared with white individuals, black men and women undergoing screening colonoscopy have a higher risk of polyps sized more than 9 mm, and black individuals older than 60 years are more likely to have proximal polyps sized more than 9 mm.

The Effect of Antireflux Surgery on Esophageal Carcinogenesis in Patients With Barrett Esophagus: A Systematic Review

Objective:To determine whether patients with Barrett esophagus who undergo antireflux surgery differ from medically treated patients in incidence of esophageal adenocarcinoma and probability of disease regression/progression. Summary Background Data:Barrett esophagus is a risk factor for the development of esophageal adenocarcinoma. A question exists as to whether antireflux surgery reduces this risk. Methods:Query of PubMed (1966 through October 2005) using predetermined search terms revealed 2011 abstracts, of which 100 full-text articles were reviewed. Twenty-five articles met selection criteria. A review of article references and consultation with experts revealed additional articles for inclusion. Studies that enrolled adults with biopsy-proven Barrett esophagus, specified treatment-type rendered, followed up patients with endoscopic biopsies no less than12 months of instituting therapy, and provided adequate extractable data. The incidence of adenocarcinoma and the proportion of patients developing progression or regression of Barrett esophagus and/or dysplasia were extracted. Results:In surgical and medical groups, 700 and 996 patients were followed for a total of 2939 and 3711 patient-years, respectively. The incidence rate of esophageal adenocarcinoma was 2.8 (95% confidence interval, 1.2–5.3) per 1000 patient-years among surgically treated patients and 6.3 (3.6–10.1) among medically treated patients (P = 0.034). Heterogeneity in incidence rates in surgically treated patients was observed between controlled studies and case series (P = 0.014). Among controlled studies, incidence rates were 4.8 (1.7–11.1) and 6.5 (2.6–13.8) per 1000 patient-years in surgical and medical patients, respectively (P = 0.320). Probability of progression was 2.9% (1.2–5.5) in surgical patients and 6.8% (2.6–12.1) in medical patients (P = 0.054). Probability of regression was 15.4% (6.1–31.4) in surgical patients and 1.9% (0.4–7.3) in medical patients (P = 0.004). Conclusions:Antireflux surgery is associated with regression of Barrett esophagus and/or dysplasia. However, evidence suggesting that surgery reduces the incidence of adenocarcinoma is largely driven by uncontrolled studies.

Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators

AIMS To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.

Lipoic acid in multiple sclerosis: a pilot study

Lipoic acid (LA) is an antioxidant that suppresses and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAM-1) of oral LA in patients with MS. Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg LA had substantially higher peak serum LA levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum LA levels and mean changes in serum MMP-9 levels (τ=-0.263, P=0.04). There was a significant dose response relationship between LA and mean change in serum sICAM-1 levels (P=0.03). We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.

Office-Based Unsedated Small-Caliber Endoscopy Is Equivalent to Conventional Sedated Endoscopy in Screening and Surveillance for Barrett's Esophagus: A Randomized and Blinded Comparison

OBJECTIVES:A major limitation to screening and surveillance of Barretts esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative.METHODS:Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barretts esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barretts esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures.RESULTS:The prevalence of Barretts esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy (P = 0.503). The level of agreement between the two approaches was “moderate” (κ = 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy (P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy.CONCLUSIONS:Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barretts esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application.

Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476.

Prevalence of polyps greater than 9 mm in a consortium of diverse clinical practice settings in the United States

BACKGROUND & AIMS Colonoscopy is often performed with the goal of identification of patients with serious colon neoplasia. We determined the prevalence of colon masses or polyps greater than 9 mm on the basis of age, gender, race, and procedure indication in diverse clinical practice settings and compared occurrence in patients receiving colonoscopy for screening, surveillance, or evaluation of symptoms. METHODS We obtained patient demographics, procedure indication, and endoscopic findings from colonoscopy reports in the Clinical Outcomes Research Initiative data repository, which receives endoscopy reports from 73 diverse practice sites in the United States. A multivariate model was developed to measure risk variables for a mass or polyps >9 mm. Absolute risk was calculated in the model on the basis of the number needed to endoscope (NNE) to identify 1 patient with a mass or polyp >9 mm. RESULTS From 2000-2002, colonoscopies in 141,413 unique patients were analyzed. Sixty-nine percent of the reports came from private practice (nonacademic) settings. Increasing age, male gender, and black race were associated with increased risk of mass or polyps >9 mm. In the 50- to 59-year-old average-risk group, 28 women and 18 men would need to have screening colonoscopy to identify 1 patient with a mass/polyp >9 mm. Patients with positive fecal occult blood test results, hematochezia, and anemia had lower NNE, whereas men older than 60 years receiving adenoma surveillance and patients with irritable bowel symptoms had similar NNE compared with average-risk subjects. CONCLUSIONS The prevalence of a colon lesion >9 mm varies on the basis of age, gender, race, and procedure indication. Understanding utilization and outcomes can lead to more optimal use of colonoscopy.